Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU

Menglin He,Weiqian Tian,Liqiu Li,Meijuan Chen,Cheng Hu,Qian Gao

doi:10.1007/s11418-021-01571-5

Menglin He, Weiqian Tian + Show 4 more

Open Access

https://doi.org/10.1007/s11418-021-01571-5

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Abstract

Acute gouty arthritis is a self-limiting inflammatory disease resulting from the deposition of monosodium urate (MSU) crystals. It has been shown that Gentiopicroside (GPS) possesses anti-inflammatory and analgesic functions. The aim of this study was to parse out whether GPS has an effect on acute gouty arthritis. We established an acute gouty arthritis model by the injection of MSU into the paw, and found that GPS relieves MSU-induced mechanical, thermal hyperalgesia, and paw swelling. Furthermore, GPS down-regulated the release of pro-inflammatory cytokines in paw tissues, including IL-1β, IL-6, IL-18, and TNF-α. The results of H&E staining and MPO activity measurement showed that GPS inhibits neutrophil infiltration. And the over-expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 induced by MSU were inhibited by treatment with GPS. These results revealed that GPS can treat acute gouty arthritis based on anti-inflammatory and analgesic properties in vivo, which might be ascribed to the inhibition on NLRP3 inflammasome. Furthermore, we performed in vitro study to confirm the results of in vivo study. Consistently, the results proved that GPS could inhibit the activation of NLRP3 inflammasome in RAW264.7 macrophages stimulated by LPS-MSU. In conclusion, this study provides an experimental basis for the application of GPS and expands the potential value of GPS in the therapy of acute gouty arthritis.

Highlights

Gout is a common and reversible auto-inflammatory disease, which is characterized by the disorder of the innate immune and causes systemic inflammatory response [1]
We established acute gouty arthritis model induced by monosodium urate (MSU) to analyze the effects of GPS on these signs
The results showed that the severity of pain induced by MSU achieved its peak at 8 h after stimulus

Summary

Introduction

Gout is a common and reversible auto-inflammatory disease, which is characterized by the disorder of the innate immune and causes systemic inflammatory response [1]. It has been reported that gout is the most conventional type of inflammatory arthritis globally [2]. High concentration of urate is identified as the key factor required for MSU. Menglin He and Cheng Hu contributed to this work. MSU crystals are first phagocytized by macrophages, and promote the assembly and activation of NLRP3 inflammasome [8]. IL-1β elevates the expression of genes, which are related to fever, pain threshold, and promote immune cells to infiltrate infected or damaged tissues [11]. Research [13] demonstrated that multiple pro-inflammatory cytokines, such as IL-6 and TNF-α, are related to gouty arthritis.

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